PNN matrices are comprised of A) non-sulfated (0S-CS), mono-sulfated (4S-CS, 6S-CS) and di-sulfated (2S6S-, 4S6S-CS) isomers. 9-month-old PS19 mice exhibit B) decreased mono-sulfated 6S-CS isomer and increased 2S6S-CS isomer compared to controls, which is visualized in C) the illustration representing flux through the 2S6S-CS isomer biosynthesis branch. These isomer changes occur in association with D) loss of WFA (PNN CS-GAGs) and gain of E) AT8 (pTau), F) GFAP (astrogliosis), and G) Iba1 (microgliosis). Statistics reported in Supplemental Tables 5
and
6.